The I domain of integrin LFA-1 interacts with ICAM-1 domain 1 at residue Glu-34 but not Gln-73.
Using a solid phase assay, we show that isolated LFA-1 I domain binds ICAM-1 in a Mg2+-dependent manner and is blocked by anti-I domain monoclonal antibodies. This activity mirrors that of the intact receptor (Dransfield, I., Cabañas, C., Craig, A., and Hogg, N. (1992) J. Cell Biol. 116, 219-226) and suggests that the I domain controls divalent cation-dependent receptor function. In ICAM-1, domain 1 residues Glu-34 and Gln-73 have been identified as critical for binding of LFA-1 as an intact receptor (Staunton, D. E., Dustin, M. L., Erickson, H. P., and Springer, T. A. (1990) Cell 61, 243-254). For the first time, we show that isolated I domain binds to domain 1 of ICAM-1 and that this interaction is inhibited partially by mutation of Glu-34 but not by Gln-73. The anti-ICAM-1 monoclonal antibody RR1/1, which maps to Gln-73 (Staunton, D. E., Dustin, M. L., Erickson, H. P., and Springer, T. A. (1990) Cell 61, 243-254), enhances I domain binding, suggesting potential allosteric control or coordinate binding by this region. Finally, I domain binding inhibited by Glu-34 ICAM-1 mutation correlates with divalent cation dependence, indicating that this residue might be in direct contact with the metal ion-dependent adhesion site. Thus, we describe the interaction between the LFA-1 I domain and ICAM-1, an event that controls the function of the intact receptor but includes only part of the complete ligand binding site.
Stanley
P
P
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.
Hogg
N
N
D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002413:Cations, Divalent; D004797:Enzyme-Linked Immunosorbent Assay; D018698:Glutamic Acid / Q000378:metabolism*; D005998:Glycine / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed
D002413:Cations, Divalent; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D018698:Glutamic Acid; D005998:Glycine